Cápsulas de tipranavir: validação de método indicativo de estabilidade por eletroforese capilar de zona e identificação de produtos de oxidação
Autor(a) principal: | |
---|---|
Data de Publicação: | 2017 |
Tipo de documento: | Dissertação |
Idioma: | por |
Título da fonte: | Repositório Institucional Manancial UFSM |
Texto Completo: | http://repositorio.ufsm.br/handle/1/18672 |
Resumo: | Tipranavir (TPV) is one of the newest drugs of the protease inhibitors class, which is indicated to patients with human immunodeficiency virus, who present therapeutic failure to other antiretrovirals of this class. It is available as a 250 mg capsule and 100 mg.mL-1 oral solution. Although commercially available since 2005, are not yet available in pharmacopoeias analytical methods for drug analysis in raw materials and formulations, as well as studies on its stability. The objective of this study was to develop and validate a quantitative capillary zone electrophoresis method for the analysis of TPV in capsules and to identify possible degradation products obtained by forced degradation studies. The reference substance was characterized by infrared spectrophotometry, ultraviolet spectrophotometry and high resolution mass spectrometry. Additionally, an impurity evidenced in the active pharmaceutical ingredient was identified by high resolution mass spectrometry and consisted of a product related to the oxidation of the TPV. The method developed met the current requirements, presenting linearity in the range of 20 to 200 μg mL-1, accuracy (recovery percentage of 100.50% ± 1.57%, n = 9), precision (interday RSD = 1.59%, n = 12), and specificity, which was evidenced by the peak purity in forced degradation studies. Robustness was assessed by 23 factorial design factorial and the results indicated that the method is robust even with small modifications in voltage, temperature and buffer concentration. By the forced degradation study, it was evidenced that the oxidation is the faster route of TPV degradation. Thus, the kinetics of degradation in oxidizing medium was determined, and the major degradation product in that condition was identified. In view of the results, care in the choice of excipients and packages is relevant to avoid oxidation of the drug. |
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2019-10-24T20:30:09Z2019-10-24T20:30:09Z2017-08-24http://repositorio.ufsm.br/handle/1/18672Tipranavir (TPV) is one of the newest drugs of the protease inhibitors class, which is indicated to patients with human immunodeficiency virus, who present therapeutic failure to other antiretrovirals of this class. It is available as a 250 mg capsule and 100 mg.mL-1 oral solution. Although commercially available since 2005, are not yet available in pharmacopoeias analytical methods for drug analysis in raw materials and formulations, as well as studies on its stability. The objective of this study was to develop and validate a quantitative capillary zone electrophoresis method for the analysis of TPV in capsules and to identify possible degradation products obtained by forced degradation studies. The reference substance was characterized by infrared spectrophotometry, ultraviolet spectrophotometry and high resolution mass spectrometry. Additionally, an impurity evidenced in the active pharmaceutical ingredient was identified by high resolution mass spectrometry and consisted of a product related to the oxidation of the TPV. The method developed met the current requirements, presenting linearity in the range of 20 to 200 μg mL-1, accuracy (recovery percentage of 100.50% ± 1.57%, n = 9), precision (interday RSD = 1.59%, n = 12), and specificity, which was evidenced by the peak purity in forced degradation studies. Robustness was assessed by 23 factorial design factorial and the results indicated that the method is robust even with small modifications in voltage, temperature and buffer concentration. By the forced degradation study, it was evidenced that the oxidation is the faster route of TPV degradation. Thus, the kinetics of degradation in oxidizing medium was determined, and the major degradation product in that condition was identified. In view of the results, care in the choice of excipients and packages is relevant to avoid oxidation of the drug.O tipranavir (TPV) é um dos mais novos fármacos da classe dos inibidores de protease, indicado para pacientes portadores do vírus da imunodeficiência humana que apresentam falha terapêutica a outros antirretrovirais dessa classe. É disponibilizado como cápsula mole de 250 mg e solução oral de 100 mg mL-1. Embora seja comercializado desde 2005, ainda são inexistentes em farmacopeias métodos analíticos para análise do fármaco em matéria-prima e formulações, assim como estudos sobre sua estabilidade. Face ao exposto, o objetivo desse trabalho foi desenvolver e validar método quantitativo por eletroforese capilar de zona para a análise do TPV em cápsulas e identificar possíveis produtos de degradação, obtidos nos estudos de degradação forçada. A substância química de referência foi caracterizada por espectrofotometria na região do infravermelho, por espectrofotometria na região do ultravioleta e por espectrometria de massas de alta resolução. Adicionalmente, realizou-se a identificação de uma impureza evidenciada na matéria-prima por espectrometria de massas de alta resolução, tendo sido constatado que a impureza consiste em um produto decorrente da oxidação do TPV. O método de doseamento desenvolvido atendeu os requisitos vigentes, tendo apresentado linearidade na faixa de 20 a 200 μg mL-1, exatidão (percentual de recuperação de 100,50% ± 1,57%, n=9), precisão (DPR entre-dias = 1,59%, n=12), e seletividade, sugerida pela pureza dos picos do analito nos estudos de degradação forçada. A robustez foi avaliada por ensaio fatorial (23), e os resultados indicaram que o método é robusto frente a pequenas modificações na voltagem, temperatura e concentração do tampão. Pelo estudo de degradação forçada evidenciou-se que a oxidação é a rota de degradação mais rápida do TPV. Desse modo, determinou-se a cinética de degradação em meio oxidante, e identificou-se o produto de degradação majoritário nessa condição. Face aos resultados, cuidados na escolha de adjuvantes e embalagens são relevantes para evitar a oxidação do fármaco.Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPESporUniversidade Federal de Santa MariaCentro de Ciências da SaúdePrograma de Pós-Graduação em Ciências FarmacêuticasUFSMBrasilFarmáciaAttribution-NonCommercial-NoDerivatives 4.0 Internationalhttp://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccessTipranavirEstabilidadeEletroforese capilar de zonaOxidaçãoProdutos de degradaçãoStabilityCZE methodOxidationDegradation productsCNPQ::CIENCIAS DA SAUDE::FARMACIACápsulas de tipranavir: validação de método indicativo de estabilidade por eletroforese capilar de zona e identificação de produtos de oxidaçãoTipranavir capsules: validation of a stability indicating cappilary zone electrophoresis method and identification of oxidation procuctsinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesisAdams, Andréa Inês Hornhttp://lattes.cnpq.br/6872246935204149Codevilla, Cristiane Francohttp://lattes.cnpq.br/3165544867590900Malesuik, Marcelo Donadelhttp://lattes.cnpq.br/8153279253583982http://lattes.cnpq.br/1586633100952027Lago, Matheus Wagner400300000005600c70d0919-394a-4d29-9efb-bdbe784bd19e6a990bf0-8cd1-4dc6-bda8-5212a72f33f5729c55e3-fe98-4273-ac56-6b31849f8c4f549f9437-1bd8-47cc-8e18-e95fd1feeacareponame:Repositório Institucional Manancial UFSMinstname:Universidade Federal de Santa Maria (UFSM)instacron:UFSMORIGINALDIS_PPGCF_2017_LAGO_MATHEUS.pdfDIS_PPGCF_2017_LAGO_MATHEUS.pdfDissertação de Mestradoapplication/pdf1129687http://repositorio.ufsm.br/bitstream/1/18672/1/DIS_PPGCF_2017_LAGO_MATHEUS.pdf3bd5e1129090a17db40ea8afd6c5a7e2MD51CC-LICENSElicense_rdflicense_rdfapplication/rdf+xml; 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dc.title.por.fl_str_mv |
Cápsulas de tipranavir: validação de método indicativo de estabilidade por eletroforese capilar de zona e identificação de produtos de oxidação |
dc.title.alternative.eng.fl_str_mv |
Tipranavir capsules: validation of a stability indicating cappilary zone electrophoresis method and identification of oxidation procucts |
title |
Cápsulas de tipranavir: validação de método indicativo de estabilidade por eletroforese capilar de zona e identificação de produtos de oxidação |
spellingShingle |
Cápsulas de tipranavir: validação de método indicativo de estabilidade por eletroforese capilar de zona e identificação de produtos de oxidação Lago, Matheus Wagner Tipranavir Estabilidade Eletroforese capilar de zona Oxidação Produtos de degradação Stability CZE method Oxidation Degradation products CNPQ::CIENCIAS DA SAUDE::FARMACIA |
title_short |
Cápsulas de tipranavir: validação de método indicativo de estabilidade por eletroforese capilar de zona e identificação de produtos de oxidação |
title_full |
Cápsulas de tipranavir: validação de método indicativo de estabilidade por eletroforese capilar de zona e identificação de produtos de oxidação |
title_fullStr |
Cápsulas de tipranavir: validação de método indicativo de estabilidade por eletroforese capilar de zona e identificação de produtos de oxidação |
title_full_unstemmed |
Cápsulas de tipranavir: validação de método indicativo de estabilidade por eletroforese capilar de zona e identificação de produtos de oxidação |
title_sort |
Cápsulas de tipranavir: validação de método indicativo de estabilidade por eletroforese capilar de zona e identificação de produtos de oxidação |
author |
Lago, Matheus Wagner |
author_facet |
Lago, Matheus Wagner |
author_role |
author |
dc.contributor.advisor1.fl_str_mv |
Adams, Andréa Inês Horn |
dc.contributor.advisor1Lattes.fl_str_mv |
http://lattes.cnpq.br/6872246935204149 |
dc.contributor.referee1.fl_str_mv |
Codevilla, Cristiane Franco |
dc.contributor.referee1Lattes.fl_str_mv |
http://lattes.cnpq.br/3165544867590900 |
dc.contributor.referee2.fl_str_mv |
Malesuik, Marcelo Donadel |
dc.contributor.referee2Lattes.fl_str_mv |
http://lattes.cnpq.br/8153279253583982 |
dc.contributor.authorLattes.fl_str_mv |
http://lattes.cnpq.br/1586633100952027 |
dc.contributor.author.fl_str_mv |
Lago, Matheus Wagner |
contributor_str_mv |
Adams, Andréa Inês Horn Codevilla, Cristiane Franco Malesuik, Marcelo Donadel |
dc.subject.por.fl_str_mv |
Tipranavir Estabilidade Eletroforese capilar de zona Oxidação Produtos de degradação |
topic |
Tipranavir Estabilidade Eletroforese capilar de zona Oxidação Produtos de degradação Stability CZE method Oxidation Degradation products CNPQ::CIENCIAS DA SAUDE::FARMACIA |
dc.subject.eng.fl_str_mv |
Stability CZE method Oxidation Degradation products |
dc.subject.cnpq.fl_str_mv |
CNPQ::CIENCIAS DA SAUDE::FARMACIA |
description |
Tipranavir (TPV) is one of the newest drugs of the protease inhibitors class, which is indicated to patients with human immunodeficiency virus, who present therapeutic failure to other antiretrovirals of this class. It is available as a 250 mg capsule and 100 mg.mL-1 oral solution. Although commercially available since 2005, are not yet available in pharmacopoeias analytical methods for drug analysis in raw materials and formulations, as well as studies on its stability. The objective of this study was to develop and validate a quantitative capillary zone electrophoresis method for the analysis of TPV in capsules and to identify possible degradation products obtained by forced degradation studies. The reference substance was characterized by infrared spectrophotometry, ultraviolet spectrophotometry and high resolution mass spectrometry. Additionally, an impurity evidenced in the active pharmaceutical ingredient was identified by high resolution mass spectrometry and consisted of a product related to the oxidation of the TPV. The method developed met the current requirements, presenting linearity in the range of 20 to 200 μg mL-1, accuracy (recovery percentage of 100.50% ± 1.57%, n = 9), precision (interday RSD = 1.59%, n = 12), and specificity, which was evidenced by the peak purity in forced degradation studies. Robustness was assessed by 23 factorial design factorial and the results indicated that the method is robust even with small modifications in voltage, temperature and buffer concentration. By the forced degradation study, it was evidenced that the oxidation is the faster route of TPV degradation. Thus, the kinetics of degradation in oxidizing medium was determined, and the major degradation product in that condition was identified. In view of the results, care in the choice of excipients and packages is relevant to avoid oxidation of the drug. |
publishDate |
2017 |
dc.date.issued.fl_str_mv |
2017-08-24 |
dc.date.accessioned.fl_str_mv |
2019-10-24T20:30:09Z |
dc.date.available.fl_str_mv |
2019-10-24T20:30:09Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/masterThesis |
format |
masterThesis |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://repositorio.ufsm.br/handle/1/18672 |
url |
http://repositorio.ufsm.br/handle/1/18672 |
dc.language.iso.fl_str_mv |
por |
language |
por |
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400300000005 |
dc.relation.confidence.fl_str_mv |
600 |
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dc.rights.driver.fl_str_mv |
Attribution-NonCommercial-NoDerivatives 4.0 International http://creativecommons.org/licenses/by-nc-nd/4.0/ info:eu-repo/semantics/openAccess |
rights_invalid_str_mv |
Attribution-NonCommercial-NoDerivatives 4.0 International http://creativecommons.org/licenses/by-nc-nd/4.0/ |
eu_rights_str_mv |
openAccess |
dc.publisher.none.fl_str_mv |
Universidade Federal de Santa Maria Centro de Ciências da Saúde |
dc.publisher.program.fl_str_mv |
Programa de Pós-Graduação em Ciências Farmacêuticas |
dc.publisher.initials.fl_str_mv |
UFSM |
dc.publisher.country.fl_str_mv |
Brasil |
dc.publisher.department.fl_str_mv |
Farmácia |
publisher.none.fl_str_mv |
Universidade Federal de Santa Maria Centro de Ciências da Saúde |
dc.source.none.fl_str_mv |
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